tbuckley/cabot-search huggingface dataset:
CD4 binding site immunogens elicit heterologous anti–HIV-1 neutralizing antibodies in transgenic and wild-type animals
Authors: Harry B. Gristick, Harald Hartweger, Maximilian Loewe, Jelle van Schooten, Victor Ramos, Thiago Y. Oliveira, Yoshiaki Nishimura, Nicholas S. Koranda, Abigail Wall, Kai-Hui Yao, Daniel Poston, Anna Gazumyan, Marie Wiatr, Marcel Horning, Jennifer R. Keeffe, Magnus A. G. Hoffmann, Zhi Yang, Morgan E. Abernathy, Kim-Marie A. Dam, Han Gao, Priyanthi N. P. Gnanapragasam, Leesa M. Kakutani, Ana Jimena Pavlovitch-Bedzyk, Michael S. Seaman, Mark Howarth, Andrew T. McGuire, Leonidas Stamatatos, Malcolm A. Martin, Anthony P. West, Michel C. Nussenzweig, Pamela J. Bjorkman
Journal: Science Immunology (2023)

Passive transfer of broadly neutralizing anti–HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal of HIV-1 vaccine efforts. bNAbs that target the CD4 binding site (CD4bs) on HIV-1 Env are among the most broadly active, but to date, responses elicited against this epitope in vaccinated animals have lacked potency and breadth. We hypothesized that CD4bs bNAbs resembling the antibody IOMA might be easier to elicit than other CD4bs antibodies that exhibit higher somatic mutation rates, a difficult-to-achieve mechanism to accommodate Env’s N276 gp120 N-glycan, and rare five-residue light chain complementarity-determining region 3. As an initial test of this idea, we developed IOMA germline–targeting Env immunogens and evaluated a sequential immunization regimen in transgenic mice expressing germline-reverted IOMA. These mice developed CD4bs epitope–specific responses with heterologous neutralization, and cloned antibodies overcame neutralization roadblocks, including accommodating the N276 gp120 glycan, with some neutralizing selected HIV-1 strains more potently than IOMA. The immunization regimen also elicited CD4bs-specific responses in mice containing polyclonal antibody repertoires as well as rabbits and rhesus macaques. Thus, germline targeting of IOMA-class antibody precursors represents a potential vaccine strategy to induce CD4bs bNAbs.
Ratio Fluorescent Detecting of Tryptophan and Its Metabolite 5‐Hydroxyindole‐3‐acetic Acid Relevant with Depression via Tb(III) Modified HOFs Hybrids: Further Designing Recyclable Molecular Logic Gate Connected by Back Propagation Neural Network
Authors: Kai Zhu, Xin Xu, Bing Yan
Journal: Advanced Healthcare Materials (2023)

Exploring intelligent fluorescent materials with high reliability and precision to diagnose diseases is significant but remains a great challenge. Herein, based on coordination post-synthetic modification, a Tb3+ functionalized ME-PA (Tb@1) is prepared, which can emit brilliant green fluorescence through ligand-to-mental charge transfer-assisted energy transfer (LMCT-ET) process from ME-PA to Tb3+ ions. Tb@1 can simultaneously distinguish Tryptophan (Try) and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA), two effective indicators for depression, in ratio and colorimetric mode. And this sensor behaves the advantages of high efficiency and sensitivity, as well as excellent reusability and anti-interference. The PET process from ME to Try and 5-HIAA, and the competitive absorption between analytes and Tb@1 may be relevant to sensing mechanism. In realistic serum or urine environment, the detection limits of Tb@1 for Try and 5-HIAA are 0.0183 and 0.0149 mg L-1 respectively. Moreover, in conjunction with back propagation neural network (BPNN), two dual-output molecular logic gates that can be calculated circularly are further designed, which realizes intelligent control of the electronic component to identify the existence of two biomarkers and judge their concentrations from fluorescence images. This work offers a novel approach to modulate logic circuits based on ML-assisted HOF fluorescent sensor, with promising application for a precise and pictorial depression diagnosis.
Trends in incidence, treatment and survival of Merkel cell carcinoma in England 2004–2018: a cohort study
Authors: Khaylen Mistry, Nick J Levell, Loes Hollestein, Marlies Wakkee, Tamar Nijsten, Craig S Knott, Neil M Steven, Paul J Craig, Zoe C Venables
Journal: British Journal of Dermatology (2022)

Merkel cell carcinoma (MCC) is a rare tumour with neuroendocrine differentiation and high associated mortality. Studies that describe the epidemiology of MCC are often limited by small sample size, short duration of follow-up, absence of nationwide data and paucity of data on different risk factors.To determine the incidence, demographics and survival for MCC in England between 2004 and 2018.This national retrospective cohort study identified all cases of MCC in England from 2004 to 2018 using national population-based data from the National Disease Registration Service. Crude counts, European age-standardized incidence rates (EASRs) and joinpoint analysis were conducted. Patient demographics and treatments received were described. Multivariable Cox regression analysis was used to study risk factors for MCC-specific mortality, by including a priori defined demographic factors, tumour characteristics and immunosuppression. Treatment data were not included in the Cox regression analysis.A total of 3775 MCC tumours were registered. The median age at diagnosis was 81 years (interquartile range 74-87). Overall, 96·6% of patients identified as White ethnicity, and 8·3% of patients were immunosuppressed. The most common site was the face (27·4%). Patients most often presented with stage one disease (22·8%); however, stage was unknown in 31·0%. In total, 80·7% of patients underwent surgical excision, 43·5% radiotherapy and 9·2% systemic therapy. The EASR increased from 0·43 per 100 000 person-years (PYs) to 0·65 per 100 000 person-years between 2004 and 2018, representing a significant annual percentage change of 3·9%. The EASR was greater in men than in women for all years, with an overall male-to-female ratio of 1·41 : 1. The highest EASR was in South West England. Five-year disease-specific survival was 65·6% [95% confidence interval (CI) 63·8-67·4], with a median follow-up of 767 days. MCC-specific mortality increased with age [hazard ratio (HR) 1·02, 95% CI 1·02-1·03], deprivation (HR 1·43, 95% CI 1·16-1·76), immunosuppression (HR 2·80, 95% CI 2·34-3·34) and stage at diagnosis (HR 8·24, 95% CI 5·84-11·6).This study presents the largest national MCC dataset in Europe, and the most complete reporting of MCC incidence and survival ever published. With the EASR of MCC increasing and high associated mortality, this study encourages further research into the pathology, diagnosis and therapeutic options for MCC to support management guidelines.
Itching and treatments in atopic dermatitis (AD): results from the German AD registry TREATgermany
Authors: Elke Weisshaar, Philipp Bentz, Eva Haufe, Luise  Heinrich, Christian Apfelbacher, Annice  Heratizadeh, Susanne Abraham, Inken Harder, Andreas Kleinheinz, Andreas  Wollenberg, Knut Schäkel, Franca  Wiemers, Konstantin Ertner, Matthias  Augustin, Julia Wildberger, Ralph  von Kiedrowski, Margitta  Worm, Alexander  Zink, Isaak Effendy, Andrea  Asmussen, Mario  Pawlak, Michael  Sticherling, Melanie  Hilgers, Christiane Handrick, Sven  Quist, Beate  Schwarz, Magnus  Bell, Petra Staubach-Renz, Su-Hei Hong-Weldemann, Bernhard Homey, Jens  Bruecher, Stephan Weidinger, Thomas  Werfel, Jochen Schmitt
Journal: British Journal of Dermatology (2022)
Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria
Authors: Quentin Philippot, Masato Ogishi, Jonathan Bohlen, Julia Puchan, Andrés Augusto Arias, Tina Nguyen, Marta Martin-Fernandez, Clement Conil, Darawan Rinchai, Mana Momenilandi, Seyed Alireza Mahdaviani, Mohammad Keramatipour, Jérémie Rosain, Rui Yang, Taushif Khan, Anna-Lena Neehus, Marie Materna, Ji Eun Han, Jessica Peel, Federico Mele, Marc Weisshaar, Sandra Jovic, Paul Bastard, Romain Lévy, Tom Le Voyer, Peng Zhang, Majistor Raj Luxman Maglorius Renkilaraj, Carlos A. Arango-Franco, Simon Pelham, Yoann Seeleuthner, Mathieu Pochon, Manar Mahmoud Ahmad Ata, Fatima Al Ali, Mélanie Migaud, Camille Soudée, Tatiana Kochetkov, Anne Molitor, Raphael Carapito, Seiamak Bahram, Bertrand Boisson, Claire Fieschi, Davood Mansouri, Nico Marr, Satoshi Okada, Mohammad Shahrooei, Nima Parvaneh, Zahra Chavoshzadeh, Aurélie Cobat, Dusan Bogunovic, Laurent Abel, Stuart G. Tangye, Cindy S. Ma, Vivien Béziat, Federica Sallusto, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Jean-Laurent Casanova, Anne Puel
Journal: Science Immunology (2023)

Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due to impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) due to impaired IL-17A/F production. We report six patients from four kindreds with AR IL-23R deficiency. These patients are homozygous for one of four different loss-of-function IL23R variants. All six patients have a history of MSMD, but only two suffered from CMC. We show that IL-23 induces IL-17A only in MAIT cells, possibly contributing to the incomplete penetrance of CMC in patients unresponsive to IL-23. By contrast, IL-23 is required for both baseline and Mycobacterium -inducible IFN-γ immunity in both Vδ2 + γδ T and MAIT cells, probably contributing to the higher penetrance of MSMD in these patients. Human IL-23 appears to contribute to IL-17A/F–dependent immunity to Candida in a single lymphocyte subset but is required for IFN-γ–dependent immunity to Mycobacterium in at least two lymphocyte subsets.
Hybrid Extracellular Vesicles‐Liposomes Camouflaged Magnetic Vesicles Cooperating with Bioorthogonal Click Chemistry for High‐Efficient Melanoma Circulating Tumor Cells Enrichment
Authors: Ke Kang, Yujia Zhang, Xiaoxi Zhou, Yue Yu, Nanhang Zhu, Jia Cheng, Qiangying Yi, Yao Wu
Journal: Advanced Healthcare Materials (2023)

Abstract The capture of melanoma circulating tumor cells (melanoma CTCs, MelCTCs) is of great significance for the early diagnosis and personalized treatment of melanoma. The rarity and heterogeneity of MelCTCs have greatly limited the development of MelCTCs capture methods, especially those based on immune/aptamer‐affinity. Herein, an extracellular vesicles‐camouflaged strategy is designed to functionalize the magnetic nanoparticles (Fe 3 O 4 ) and to generate magnetic vesicles (Fe 3 O 4 @lip/ev) with excellent antifouling and active tumor cell targeting properties. Combined with the bioorthogonal click chemistry, the engineered magnetic vesicles with dibenzocyclooctyne can be widely used to target and separate all the metabolically labeled CTCs with varied phenotypes, organ origin, and even the biological species. The capture efficiency exceeded 80% with an extremely low detection limitation of ten cells. Most importantly, the strategy proposed can be directly applied to enrich MelCTCs from 0.5 mL blood samples of melanoma‐bearing mice, with a greatly minimized residue of white blood cells (only 21–568) while ignoring the fluctuations of MelCTC phenotype.
Multi-layer-structured bioactive glass nanopowder for multistage-stimulated hemostasis and wound repair
Authors: Yidan Wang, Meng luo, Ting Li, Chenxi Xie, Sihua Li, Bo Lei
Journal: Bioactive Materials (2023)

Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis, inflammation regulation, and skin tissue remodeling into the one system instead of single-stage boosting. In this work, a multilayer-structured bioactive glass nanopowder (BGN@PTE) is developed by coating the poly-tannic acid and ε-polylysine onto the BGN via facile layer-by-layer assembly as an integrative and multilevel dressing for the sequential management of wounds. In comparison to BGN and poly-tannic acid coated BGN, BGN@PTE exhibited the better hemostatic performance because of its multiple dependent approaches to induce the platelet adhesion/activation, red blood cells (RBCs) aggregation and fibrin network formation. Simultaneously, the bioactive ions from BGN facilitate the regulation of the inflammatory response while the poly-tannic acid and antibacterial ε-polylysine prevent the wound infection, promoting the wound healing during the inflammatory stage. In addition, BGN@PTE can serve as a reactive oxygen species scavenger, alleviate the oxidation stress in wound injury, induce the cell migration and angiogenesis, and promote the proliferation stage of wound repair. Therefore, BGN@PTE demonstrated the significantly higher wound repair capacity than the commercial bioglass dressing Dermlin™. This multifunctional BGN@PTE is a potentially valuable dressing for full-thickness wound management and may be expected to extend to the other wounds therapy.
A “T.E.S.T.” hydrogel bioadhesive assisted by corneal cross-linking for in situ sutureless corneal repair
Authors: Meiyan Li, Ruoyan Wei, Chang Liu, Haowei Fang, Weiming Yang, Yunzhe Wang, Yiyong Xian, Kunxi Zhang, Yong He, Xingtao Zhou
Journal: Bioactive Materials (2023)

Corneal transplantation is an effective clinical treatment for corneal diseases, which, however, is limited by donor corneas. It is of great clinical value to develop bioadhesive corneal patches with functions of "Transparency" and "Epithelium & Stroma generation", as well as "Suturelessness" and "Toughness". To simultaneously meet the "T.E.S.T." requirements, a light-curable hydrogel is designed based on methacryloylated gelatin (GelMA), Pluronic F127 diacrylate (F127DA) & Aldehyded Pluronic F127 (AF127) co-assembled bi-functional micelles and collagen type I (COL I), combined with clinically applied corneal cross-linking (CXL) technology for repairing damaged cornea. The patch formed after 5 min of ultraviolet irradiation possesses transparent, highly tough, and strongly bio-adhesive performance. Multiple cross-linking makes the patch withstand deformation near 600% and exhibit a burst pressure larger than 400 mmHg, significantly higher than normal intraocular pressure (10-21 mmHg). Besides, the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo, supporting the regrowth of corneal epithelium and stroma. The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks, showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.
Reply to Francesco Montorsi, Simone Scuderi, Alberto Briganti, and Giorgio Gandaglia’s Letter to the Editor re: Melline G.M. Schilham, Mark Rijpkema, Tom Scheenen, et al. How Advanced Imaging Will Guide Therapeutic Strategies for Patients with Newly Diagnosed Prostate Cancer in the Years to Come. Eur Urol 2022;82:578–80
Authors: Melline G.M. Schilham, Mark Rijpkema, Tom Scheenen, Rick Hermsen, Jelle O. Barentsz, J.P.Michiel Sedelaar, Heidi Kusters-Vandevelde, Linda G.W. Kerkmeijer, Diederik M. Somford, Martin Gotthardt
Journal: European Urology (2023)
The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms
Authors: Jie Chen, Xiaohong Wei, Qian Zhang, Yuzhuo Wu, Guiyang Xia, Huan Xia, Lingyan Wang, Hongcai Shang, Sheng Lin
Journal: Acta Pharmaceutica Sinica B (2023)

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.
Myeloid dendritic cells are increased in the lesional skin and associated with pruritus in patients with prurigo nodularis
Authors: Taoming Liu, Yuqi Chu, Sheng Li, Yuqian Wang, Xinyue Zhong, Hong Fang, Jianjun Qiao
Journal: MedComm (2023)

The number of dermal mDCs (CD11c+ cells) was increased with itch intensity (r = 0.886, p = 0.003) using immunofluorescence (IF). On IF, CD11c+ mDCs expressed IL-31 in lesional PN skin. Fluorescence in situ hybridization combined with IF also confirmed IL-31 mRNA expression by mDCs in PN lesion. Higher population of colocalization of CD11c+ mDCs expressing IL-31 mRNA were more than CD68+ macrophages and CD3+ T cells in consecutive sections of PN skin lesion. HC, healthy control; PN, prurigo nodularis; SPN, PN with severe pruritus (itch NRS score ≥7 points); MPN, PN with mild pruritus (itch NRS score <3 points); NRS, Numeric Rating Scale; AD, atopic dermatitis; mDC, myeloid dendritic cell.
Activated macrophage membrane-coated nanoparticles relieve osteoarthritis-induced synovitis and joint damage
Authors: Kai Zhou, Chengli Yang, Kun Shi, Yue Liu, Danrong Hu, Xinlong He, Yun Yang, Bingyang Chu, Jinrong Peng, Zongke Zhou, Zhiyong Qian
Journal: Biomaterials (2023)
How do fishes manage disease?
Authors: David B. Vaughan, Richard J. Saunders, Kate S. Hutson
Journal: Trends in Ecology & Evolution (2023)

Disease drives the evolution of proactive and reactive mitigation behaviours in fishes as for terrestrial animals. Understanding fish self-remedy behaviours could discover algal bioactives, reveal novel strategies for disease management, identify new habitats or ecosystems critical to population health and conservation, and enhance knowledge of interspecific evolutionary relationships and communication.
Selective ischemic-hemisphere targeting Ginkgolide B liposomes with improved solubility and therapeutic efficacy for cerebral ischemia-reperfusion injury
Authors: Yang Li, Miaomiao Zhang, Shiyi Li, Longlong Zhang, Jisu Kim, Qiujun Qiu, Weigen Lu, Jianxin Wang
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Cerebral ischemia-reperfusion injury (CI/RI) remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies. One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier (BBB), which affects the intracerebral delivery of drugs. Ginkgolide B (GB), a major bioactive component in commercially available products of Ginkgo biloba, has been shown significance in CI/RI treatment by regulating inflammatory pathways, oxidative damage, and metabolic disturbance, and seems to be a candidate for stroke recovery. However, limited by its poor hydrophilicity and lipophilicity, the development of GB preparations with good solubility, stability, and the ability to cross the BBB remains a challenge. Herein, we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid (DHA) to obtain a covalent complex GB-DHA, which can not only enhance the pharmacological effect of GB, but can also be encapsulated in liposomes stably. The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion (MCAO) rats. Compared to the marketed ginkgolide injection, Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion. Low levels of reactive oxygen species (ROS) and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment, while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype, which modulate neuroinflammatory and angiogenesis. In addition, Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway. Thus, transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
Integrated Nanorod‐Mediated PD‐L1 Downregulation in Combination with Oxidative‐Stress Immunogene Therapy against Cancer
Authors: Shuaiying Wu, Jianzhong Zhang, Jie Pan, Shuang Bai, Ziying Wang, Yulun Chen, Dazhuang Xu, Yibo An, Chao Liu, Chengchao Chu, Qixuan Dai, Lai Jiang, Zhixiang Lu, Gang Liu
Journal: Advanced Healthcare Materials (2023)

It is an engaging program for tumor treatment that rationalizes the specific microenvironments, activation of suppressed immune system (immune resistance/escape reversion), and synergistic target therapy. Herein, a biomimetic nanoplatform that combines oxidative stress with genetic immunotherapy to strengthen the therapeutic efficacy is developed. Ru-TePt nanorods, small interfering RNA (PD-L1 siRNA), and biomimetic cellular membrane vesicles with the targeting ability to design a multifunctional Ru-TePt@siRNA-MVs system are rationally integrated. Notably, the Fenton-like activity significantly enhances Ru-TePt nanorods sonosensitization, thus provoking stronger oxidative stress to kill cells directly. Meanwhile, immunogenic cell death is triggered to secrete numerous cytokines and activate T cells. The effective catalase characteristics of Ru-TePt enable the in situ oxygen-producing pump to improve tumor oxygen level and coordinately strengthen the therapeutic effect of SDT followed. More importantly, anti-PD-L1-siRNA mediated immune checkpoint silence of the PD-L1 gene creates an environment conducive to activating cytotoxic T lymphocytes, synergistic with boosted reactive oxygen species-triggered antitumor immune response. The experimental results in vitro and in vivo reveal that the Ru-TePt@siRNA-MVs nanosystems can effectively activate the oxidative stress-triggered immune response and inhibit PD-1/PD-L1 axis-mediated immune resistance. Consequently, this orchestrated treatment paradigm provides valuable insights for developing potential oxidative stress and genetic immunotherapy.
Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment
Authors: Fei Jiang, Xuanyu Qi, Xiaolin Wu, Sihan Lin, Junfeng Shi, Wenjie Zhang, Xinquan Jiang
Journal: Bioactive Materials (2023)

Bone morphogenetic protein (BMP-2) has been approved by the FDA to promote bone regeneration, but uncertain osteogenic effect and dose-dependent side effects may occur. Osteoimmunomodulation plays an important role in growth factor-based osteogenesis. Here, we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2. We observed that the expression level of local IL-1β did not increase with the dose of BMP-2 in the mouse osteogenesis model. A low dose of BMP-2 could not promote new bone formation, but trigger the release of IL-1β from M1 macrophages. As the dose of BMP-2 increased, the IL-1β expression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2, and new bone tissues formed, even excessively. Anti-inflammatory drugs (Dexamethasone, Dex) promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation. Thus, we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands, including IL-1β and IL-1Ra. The dose of BMP-2 could be reduced by introducing immunoregulatory strategies.